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Publication year
2018Source
American Journal of Physiology : Renal Physiology, 315, 4, (2018), pp. F1129-F1138ISSN
Publication type
Article / Letter to editor

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Organization
Physiology
Journal title
American Journal of Physiology : Renal Physiology
Volume
vol. 315
Issue
iss. 4
Page start
p. F1129
Page end
p. F1138
Subject
Radboudumc 11: Renal disorders RIMLS: Radboud Institute for Molecular Life SciencesAbstract
Fine-tuning of the body's water balance is regulated by vasopressin (AVP), which induces the expression and apical membrane insertion of aquaporin-2 water channels and subsequent water reabsorption in the kidney. Here we demonstrate that silencing of microRNA-132 (miR-132) in mice causes severe weight loss due to acute diuresis coinciding with increased plasma osmolality, reduced renal total and plasma membrane expression of aquaporin-2, and abrogated increase in AVP levels. Infusion with synthetic AVP fully reversed the antagomir-132-induced diuresis, and low-dose intracerebroventricular administration of antagomir-132 similarly caused acute diuresis. Central and intracerebroventricular antagomir-132 injection both decreased hypothalamic AVP mRNA levels. At the molecular level, antagomir-132 increased the in vivo and in vitro mRNA expression of methyl-CpG-binding protein-2 (MECP2), which is a miR-132 target and which blocks AVP gene expression by binding its enhancer region. In line with this, treatment of hypothalamic N6 cells with a high-salt solution increased its miR-132 levels, whereas it attenuated endogenous Mecp2 mRNA levels. In conclusion, we identified miR-132 as a first miRNA regulating the osmotic balance by regulating the hypothalamic AVP gene mRNA expression.
This item appears in the following Collection(s)
- Academic publications [227437]
- Electronic publications [107154]
- Faculty of Medical Sciences [86157]
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